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1.
Chemosphere ; 240: 124900, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31563099

RESUMO

Spirotetramat (SPT) is a new tetronic acid derivative insecticide used to control scales and aphids; the potential for endocrine disruptor effects in fish could not be finalized with the available data. In this study, zebrafish were selected to assess the endocrine-disrupting effects. Significant decrease of plasma estradiol (E2), testosterone (T) and 11-ketotestosterone (11-KT) were observed in both male and female following the spirotetramat exposure; the vitellogenin (VTG) level in females significantly decreased. The expression of the hypothalamic-pituitary-gonad (HPG) axis genes fshr, lhr and esr1 showed significant increase in the gonads, which expression in males is higher than in females. In addition, the activities of capspase-3 and caspase-9 significantly decreased in both males and females liver, while the capspase-3 and caspase-9 were increased in male testis, the mRNA expression levels of genes expression related to the apoptosis pathway were also significantly altered after the spirotetramat exposure. Additionally, we found the parental zebrafish exposed to spirotetramat induced the development delay of its offspring. Above all, the adverse effects induced by spirotetramat suggesting that spirotetramat is a potential exogenous hazardous agent.

2.
J Cell Biochem ; 121(1): 135-141, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31578769

RESUMO

MicroRNA-132 (miR-132) has been shown to participate in many diseases. This study aimed to understand the correlation between the level of miR-132 and the severity of dementia post-ischemic stroke. An online tool (www.mirdb.org) was used to find the miR-132 binding site in acetylcholinesterase (ACHE) 3'-untranslated region (UTR), followed by a luciferase reporter assay to validate ACHE as a miR-132 target. A similar relationship between miR-132 and ACHE was also established in cerebrospinal fluid samples collected from human subjects. A negative correlation was established between ACHE and miR-132 by measuring the relative luciferase activity. Meanwhile, Western blot analysis and real-time polymerase chain reaction were also conducted to compare the levels of ACHE messenger RNA and protein between two groups (dementia positive, n = 26 and dementia negative, n = 26) or among cells treated with miR-132 mimics, ACHE small interfering RNA, and miR-132 inhibitors. As shown in the results, miR-132 can reduce the expression of ACHE. Further experiments were also carried out to study the effect of miR-132 and ACHE on cell viability and apoptosis, and the results demonstrated that miR-132 enhanced cell viability while suppressing apoptosis. In addition, ACHE reduced cell viability while promoting apoptosis. miR-132 targeted ACHE and suppressed its expression. Additionally, miR-132 and ACHE have been shown to affect the cell viability and apoptosis in the central nervous system.

3.
Ann Anat ; 227: 151418, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31626903

RESUMO

The present study aims to provide anatomical evidence for clinical application of the medial sural artery perforator (MSAP) flap. The current study investigated the vascular anatomy of the flap, evaluated the postoperative appearance and function of the donor and recipient sites, and investigate the clinical value in reconstruction of oral cavity. Six lower limbs of Chinese adult cadavers were microsurgically dissected. The locations and courses of the medial sural artery perforators were identified and recorded, which provided an anatomical basis for clinical application. Then, 16 clinical cases employing this flap were evaluated, ranging from 3×4cm to 6×8cm, and were employed for defects in the oral cavity region. Sixteen clinical cases with intraoral soft tissue defects, which included four clinical cases with inner cheek defects, were successfully followed up for 10-47 months (24 months on average). The donor site function, contour of recipient site and oral function recovery were evaluated as acceptable or better in cases with intraoral soft tissue defect, which were further verifying the value of clinical application of MSAP in repairing oral cavity defects. Moreover, two typical clinical cases were described in detail. To conclude, the MSAP flap is a favorable choice for small- to medium-size defects based on minor donor site morbidity, satisfactory oral function recovery, perforator stability and adaptation of the pedicle for anastomosis in the oral cavity region.

4.
Chemosphere ; 238: 124571, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31472351

RESUMO

Rhodococcus exhibits strong adaptability to environmental stressors and plays a crucial role in environmental bioremediation. However, seasonal changes in ambient temperature, especially rapid temperature drops exert an adverse effect on in situ bioremediation. In this paper, we studied the cell morphology and fatty acid composition of an aniline-degrading strain Rhodococcus sp. CNS16 at temperatures of 30 °C, 20 °C, and 10 °C. At suboptimal temperatures, cell morphology of CNS16 changed from short rod-shaped to long rod or irregular shaped, and the proportion of unsaturated fatty acids was upregulated. Transcriptomic technologies were then utilized to gain detailed insights into the adaptive mechanisms of CNS16 subjected to suboptimal temperatures. The results showed that the number of gene responses was significantly higher at 10 °C than that at 20 °C. The inhibition of peptidoglycan synthase expression and up-regulation of Filamentous Temperature Sensitive as well as unsaturated fatty acid synthesis genes at suboptimal temperatures might be closely related to corresponding changes in cell morphology and fatty acids composition. Strain CNS16 showed loss of catalase and superoxide dismutase activity, and utilized thioredoxin-dependent thiol peroxidase to resist oxidative stress. The up-regulation of carotenoid and Vitamin B2 synthesis at 10 °C might also be involved in the resistance to oxidative stress. Amino acid metabolism, coenzyme and vitamin metabolism, ABC transport, and energy metabolism are essential for peptidoglycan synthesis and regulation of cellular metabolism; therefore, synergistically resisting environmental stress. This study provides a mechanistic basis for the regulation of aniline degradation in Rhodococcus sp. CNS16 at low temperatures.

5.
Behav Sleep Med ; : 1-14, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31672062

RESUMO

Objective: Poor sleep quality is common in nursing staff. This meta-analysis aimed to examine the pooled prevalence of poor sleep quality in nursing staff.Methods: A systematic search in PubMed, EMBASE, PsycINFO, and Web of Science databases was performed. Studies that reported sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) were synthesized using a random-effects model.Results: Fifty-three studies were analyzed. The pooled prevalence of poor sleep quality was 61.0% (95% CI: 55.8-66.1%). The pooled total PSQI score was 7.13 ± 0.18 (95% CI: 6.78-7.50). The pooled component scores were 1.47 ± 0.20 (95% CI of mean score: 1.08-1.85) in sleep latency, 0.91 ± 0.15 (95% CI of mean score: 0.61-1.21) in sleep duration, 1.59 ± 0.13 (95% CI of mean score: 1.35-1.84) in overall sleep disturbances, 0.33 ± 0.18 (95% CI of mean score: 0-0.67) in sleeping medication, 1.21 ± 1.20 (95% CI of mean score: 0.83-1.60) in daytime dysfunction, 1.39 ± 0.14 (95% CI of mean score: 1.11-1.67) in subjective sleep quality, and 0.66 ± 0.11 (95% CI of mean score: 0.44-0.87) in habitual sleep efficiency. Subgroup and meta-regression analyses found that PSQI cutoff values, mean age, body mass index (BMI), sample size, study quality, and work experience moderated the prevalence of poor sleep quality.Conclusions: Poor sleep quality appears to be common in nursing staff. Considering its negative impact on health, effective measures should be taken to improve poor sleep quality in this population. Longitudinal studies should be conducted to examine the contributing factors of nurses' poor sleep quality.

6.
J Alzheimers Dis ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31683484

RESUMO

Exaggerated Ca2+ signaling might be one of primary causes of neural dysfunction in Alzheimer's disease (AD). And the intracellular Ca2+ overload has been closely associated with amyloid-ß (Aß)-induced endoplasmic reticulum (ER) stress and memory impairments in AD. Here we showed for the first time the neuroprotective effects of Xestospongin C (XeC), a reversible IP3 receptor antagonist, on the cognitive behaviors and pathology of APP/PS1 AD mice. Male APP/PS1-AD mice (n = 20) were injected intracerebroventricularly with XeC (3µmol) via Alzet osmotic pumps for four weeks, followed by cognition tests, Aß plaque examination, and ER stress-related protein measurement. The results showed that XeC pretreatment significantly improved the cognitive behavior of APP/PS1-AD mice, raising the spontaneous alteration accuracy in Y maze, decreasing the escape latency and increasing the target quadrant swimming time in Morris water maze; XeC pretreatment also reduced the number of Aß plaques and the overexpression of ER stress proteins 78 kDa glucose-regulated protein (GRP-78), caspase-12, and CAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) in the hippocampus of APP/PS1 mice. In addition, in vitro experiments showed that XeC effectively ameliorated Aß1 - 42-induced early neuronal apoptosis and intracellular Ca2+ overload in the primary hippocampal neurons. Taken together, IP3R-mediated Ca2+ disorder plays a key role in the cognitive deficits and pathological damages in AD mice. By targeting the IP3 R, XeC might be considered as a novel therapeutic strategy in AD.

7.
J Hazard Mater ; : 121461, 2019 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-31685320

RESUMO

Sulfur-containing materials are very attractive for the efficient decontamination of some heavy metals. However, the effective and irreversible removal of Cd2+, coupled with a high uptake efficiency, remains a great challenge due to the relatively low bond dissociation energy of CdS. Herein, we propose a new strategy to overcome this challenge, by the incorporation of Cd2+ into a stable ZnxCd1-xS solid solution, rather than into CdS. This can be realised through the adsorption of Cd2+ by ZnS nanoparticles, which have exhibited a Cd2+ uptake capacity of approximate 400 mg g-1. Through this adsorption mechanism, the Cd2+ concentration in a contaminated solution could effectively be reduced from 50 ppb to <3 ppb, a WHO limit acceptable for drinking water. In addition, ZnS continued to exhibit this noteworthy uptake capacity even in the presence of Cu2+, Pb2+, and Hg2+. ZnS displayed high chemical stability. Particles aged in air for 3 months still retained a> 80% uptake capacity for Cd2+, compared with only 9% uptake capacity for similarly-aged FeS particles. This work reveals a new mechanism for Cd2+ removal with ZnS and establishes a valuable starting point for further studies into the formation of solid solutions for hazardous heavy metal removal applications.

8.
Artigo em Inglês | MEDLINE | ID: mdl-31712796

RESUMO

Through air inhalation, dust ingestion and dermal exposure, the indoor environment plays an important role in controlling human chemical exposure. Indoor emissions and chemistry can also have direct impacts on the quality of outdoor air. And so, it is important to have a strong fundamental knowledge of the chemical processes that occur in indoor environments. This review article summarizes our understanding of the indoor chemistry field. Using a molecular perspective, it addresses primarily the new advances that have occurred in the past decade or so and upon developments in our understanding of multiphase partitioning and reactions. A primary goal of the article is to contrast indoor chemistry to that which occurs outdoors, which we know to be a strongly gas-phase, oxidant-driven system in which substantial oxidative aging of gases and aerosol particles occurs. By contrast, indoor environments are dark, gas-phase oxidant concentrations are relatively low, and due to air exchange, only short times are available for reactive processing of gaseous and particle constituents. However, important gas-surface partitioning and reactive multiphase chemistry occur in the large surface reservoirs that prevail in all indoor environments. These interactions not only play a crucial role in controlling the composition of indoor surfaces but also the surrounding gases and aerosol particles, thus affecting human chemical exposure. There are rich research opportunities available if the advanced measurement and modeling tools of the outdoor atmospheric chemistry community continue to be brought indoors.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31675340

RESUMO

Topological data analysis (TDA) is a powerful method for reducing data dimensionality, mining underlying data relationships, and intuitively representing the data structure. The Mapper algorithm is one such tool that projects high-dimensional data to 1-dimensional space by using a filter function that is subsequently used to reconstruct the data topology relationships. However, domain context information and prior knowledge have not been considered in current TDA modeling frameworks. Here, we report the development and evaluation of a semisupervised topological analysis (STA) framework that incorporates discrete or continuously labeled data points and selects the most relevant filter functions accordingly. We validate the proposed STA framework with simulation data and then apply it to samples from Genotype-Tissue Expression data and ovarian cancer transcriptome datasets. The graphs generated by STA for these 2 datasets, based on gene expression profiles, are consistent with prior knowledge, thereby supporting the effectiveness of the proposed framework.

10.
BMC Pregnancy Childbirth ; 19(1): 408, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31703641

RESUMO

BACKGROUND: Incarceration of the gravid uterus is a rare obstetric disorder that contributes to pregnancy-related complications. To understand its clinical characteristics and managements, we have reviewed the etiology, risk factors, clinical characteristics and current treatments of an incarcerated gravid uterus based on 162 cases reported in the English language literature, including our patient. CASE PRESENTATION: A 25-year-old primigravida, with a history of lymphatic tuberculosis, infertility due to blocked fallopian tubes and received in vitro fertilization. The patient presented with urine retention and lower abdominal pain in the early second trimester. Uterine incarceration was diagnosed based on pelvic examination and abdominal ultrasound. A Foley catheter was placed and manual reposition was successful. No episode of retention was experienced after the further enlargement of the uterus and its ascent. A healthy infant was delivered vaginally on 38th week of pregnancy. CONCLUSIONS: Uterine incarceration due to pelvic adhesions is rare and, because of it non-specific clinical presentations, is often misdiagnosed. Abdominal ultrasound is instrumental for the diagnosis because it can directly image the disturbed uterine and pelvic anatomy. There are limited treatment options for uterine incarceration, but definitive diagnosis allows procedures to treat and to reduce severe complications of uterine incarceration.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31722473

RESUMO

Quantization aims to form new vectors or matrices with shared values close to the original. In recent years, the popularity of scalar quantization has been soaring as it has been found huge utilities in reducing the resource cost of neural networks. Popular clustering-based techniques suffers substantially from the problems of dependency on the seed, empty or out-of-the-range clusters, and high time complexity. To overcome the problems, scalar quantization is examined from a new perspective, namely sparse least square optimization. Specifically, several quantization algorithms based on l1 least square are proposed and implemented. In addition, similar schemes with l1+ l2 and l0 regularization are proposed. Furthermore, to compute quantization results with given amount of values/clusters, this paper proposes an iterative method and a clustering-based method, and both of them are built on sparse least square. The algorithms proposed are tested under three data scenarios and their computational performance, including information loss, time consumption and distribution of values of sparse vectors are compared. The paper offers a new perspective to probe the area of quantization, and the algorithms proposed are superior especially under bit-width reducing scenarios, when the required post-quantization resolution is not significantly lower than the original scalar.

12.
Nucleic Acids Res ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31701131

RESUMO

Comprehensive genomic analyses of cancers have revealed substantial intrapatient molecular heterogeneities that may explain some instances of drug resistance and treatment failures. Examination of the clonal composition of an individual tumor and its evolution through disease progression and treatment may enable identification of precise therapeutic targets for drug design. Multi-region and single-cell sequencing are powerful tools that can be used to capture intratumor heterogeneity. Here, we present a database we've named CancerTracer (http://cailab.labshare.cn/cancertracer): a manually curated database designed to track and characterize the evolutionary trajectories of tumor growth in individual patients. We collected over 6000 tumor samples from 1548 patients corresponding to 45 different types of cancer. Patient-specific tumor phylogenetic trees were constructed based on somatic mutations or copy number alterations identified in multiple biopsies. Using the structured heterogeneity data, researchers can identify common driver events shared by all tumor regions, and the heterogeneous somatic events present in different regions of a tumor of interest. The database can also be used to investigate the phylogenetic relationships between primary and metastatic tumors. It is our hope that CancerTracer will significantly improve our understanding of the evolutionary histories of tumors, and may facilitate the identification of predictive biomarkers for personalized cancer therapies.

13.
Food Chem Toxicol ; : 110934, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682931

RESUMO

The novel commensal strain of Bacteroides fragilis HCK-B3 isolated from a healthy Chinese donor was discovered beneficial effects of attenuating lipopolysaccharides-induced inflammation. In order to contribute to the development of natural next-generation probiotic strains, the safety assessment was carried out with in vitro investigations of its morphology, potential virulence genes and antimicrobial resistance, and an in vivo acute toxicity study based on both healthy and immunosuppressed mice by cyclophosphamide injection. Consequently, the potential virulence genes in the genome of B. fragilis HCK-B3 have yet been identified as toxicity-associated. The absence of plasmids prevents the possibility of transferring antibiotic resistance features to other intestinal commensals. No intracorporal pathogenic properties were observed according to the body weight, hematological and liver parameters, cytokine secretions and tissue integrity. In addition, B. fragilis HCK-B3 performed alleviations on part of the side effects caused by the cyclophosphamide treatment. Thus, the novel strain of B. fragilis HCK-B3 was confirmed to be non-toxigenic and did not display adverse effects in both healthy and immune-deficient mice at a routinely applicable dose.

14.
Nanotheranostics ; 3(4): 311-330, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687320

RESUMO

Glioblastoma is one of the most common primary tumor types of central nervous system (CNS) with high malignance and lethality. Although many treatment options are currently available, the therapy of brain cancers remains challenging because of blood-brain-barrier (BBB) which prevents most of the chemotherapeutics into the CNS. In this work, a poly(amidoamine) dendrimer-based carrier was fabricated and modified with angiopep-2 (Ang2) peptide that has been demonstrated to bind to low density lipoprotein receptor-relative protein-1 (LRP1) on the endothelial cells of BBB and could therefore induce BBB penetration of the carrier. To improve tumor-targeting effect towards the glioma sites, the dendrimer was simultaneously functionalized with an epidermal growth factor receptor (EGFR)-targeting peptide (EP-1) which was screened from a "one-bead one-compound" (OBOC) combinatorial library. EP-1 peptide was demonstrated to have high affinity and specificity to EGFR at both the molecular and cellular levels. The dual-targeting dendrimer exhibited outstanding BBB penetrability and glioma targeting efficiency both in vitro and in vivo, which strikingly enhanced the anti-gliomas effect of the drugs and prolonged the survival of gliomas-bearing mice. These results show the potential of the dual-targeting dendrimer-based carrier in the therapy of gliomas through enhancing BBB penetrability and tumor targeting.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31703336

RESUMO

Background: Extraction of periodontally compromised or strategically non-important teeth is often an integral part of non-surgical periodontal treatment (NSPT). This study evaluated the association between the status of adjacent teeth and the outcome of NSPT on molars. Methods: Charting data of patients with generalized chronic periodontitis receiving NSPT in 2012-2014 were included. The association between initial clinical parameters and significant clinical improvement, including the reductions of probing pocket depth (PPD) and clinical attachment loss (CAL), in molar teeth with severe periodontitis after NSPT was assessed by a generalized linear model and logistic regression. Results: ≥7 mm PPD and <2 mm gingival recession (REC) at the tooth level, and ≥7 mm PPD, ≥7 mm CAL and <2 mm REC at the site level, were associated with significant clinical improvement. Absence or extraction of an adjacent tooth achieved an additional 0.22-0.23 mm and 0.60-0.83 mm clinical improvement. Among the interproximal sites, ≥7 mm PPD, <2 mm REC, ≥7 mm CAL,

16.
BMC Infect Dis ; 19(1): 961, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31711425

RESUMO

BACKGROUND: Clostridioides difficile is considered the main pathogen responsible for hospital-acquired infections. This prospective study determined the prevalence, molecular epidemiological characteristics, and risk factors for C. difficile infection (CDI) and C. difficile colonization (CDC) among patients in the intensive care unit (ICU) of a large-scale tertiary hospital in China, with the aim of providing strategies for efficient CDI and CDC prevention and control. METHODS: Stool samples were collected and anaerobically cultured for C. difficile detection. The identified isolates were examined for toxin genes and subjected to multilocus sequence typing. Patients were classified into CDI, CDC, and control groups, and their medical records were analyzed to determine the risk factors for CDI and CDC. RESULTS: Of the 800 patients included in the study, 33 (4.12%) and 25 (3.12%) were identified to have CDI and CDC, respectively. Associations with CDI were found for fever (OR = 13.993), metabolic disorder (OR = 7.972), and treatment with fluoroquinolone (OR = 42.696) or combined antibiotics (OR = 2.856). CDC patients were characterized by prolonged hospital stay (OR = 1.137), increased number of comorbidities (OR = 36.509), respiratory diseases (OR = 0.043), and treatment with vancomycin (OR = 18.168). Notably, treatment with metronidazole was found to be a protective factor in both groups (CDI: OR = 0.042; CDC: OR = 0.013). Eighteen sequence types (STs) were identified. In the CDI group, the isolated strains were predominantly toxin A and toxin B positive (A + B+) and the epidemic clone was genotype ST2. In the CDC group, the dominant strains were A + B+ and the epidemic clone was ST81. CONCLUSIONS: The prevalences of CDC and CDI in our ICU were relatively high, suggesting the importance of routine screening for acquisition of C. difficile. Future prevention and treatment strategies for CDC and CDI should consider hospital stay, enteral nutrition, underlying comorbidities, and use of combined antibiotics. Moreover, metronidazole may be a protective factor for both CDI and CDC, and could be used empirically.

17.
J Cell Mol Med ; 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31758636

RESUMO

Myeloid-derived growth factor (MYDGF) is a novel protein secreted by bone marrow cells that features important physiological functions. In recent years, MYDGF has gained considerable interest due to their extensive beneficial effect on cardiac repair and protects cardiomyocytes from cell death. However, its precise molecular mechanisms have not been well elucidated. The purpose of this study was to produce sufficient amount of biologically active recombinant human (rh) MYDGF more economically and effectively by using in vitro molecular cloning techniques to study its clinical application. The prokaryotic expression system of Escherichia coli was established for the preparation of rhMYDGF. Finally, a large amount of high biologically active and purified form of recombinant protein was obtained. Moreover, we investigated the potential mechanism of rhMYDGF-mediated proliferation and survival in human coronary artery endothelial cells (HCAECs). Mechanistically, the results suggested that MAPK/STAT3 and the cyclin D1 signalling pathways are indispensable for rhMYDGF-mediated HCAEC proliferation and survival. Therefore, this study successfully established a preparation protocol for biologically active rhMYDGF and it may be a most economical way to produce high-quality active rhMYDGF for future clinical application.

18.
Biomed Pharmacother ; 121: 109582, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31706100

RESUMO

Increasing evidence revealed that circular RNAs (circRNAs) play important roles in tumor progression. In the present study, we explored the roles and underlying mechanisms of hsa_circ_0075341 in cervical cancer development. Our data showed that the expression of hsa_circ_0075341 was significantly upregulated and associated with larger tumor size, advanced FIGO stage, and lymph-node metastasis in cervical cancer patients. Hsa_circ_0075341 inhibition reduced cervical cancer cell proliferation and invasion in vitro. In mechanism, hsa_circ_0075341 negatively regulated miR-149-5p in cervical cancer progression. In addition, AURKA was confirmed as a direct target of miR-149-5p in cervical cancer and positively regulated by hsa_circ_0075341. Collectively, our data suggested that hsa_circ_0075341 promoted cervical cancer cell proliferation and invasion through regulating the miR-149-5p/AURKA axis, which provided a novel therapeutic target for cervical cancer treatment.

19.
Small ; : e1903296, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31709707

RESUMO

Irinotecan is one of the main chemotherapeutic agents for colorectal cancer (CRC). MicroRNA-200 (miR-200) has been reported to inhibit metastasis in cancer cells. Herein, pH-sensitive and peptide-modified liposomes and solid lipid nanoparticles (SLN) are designed for encapsulation of irinotecan and miR-200, respectively. These peptides include one cell-penetrating peptide, one ligand targeted to tumor neovasculature undergoing angiogenesis, and one mitochondria-targeting peptide. The peptide-modified nanoparticles are further coated with a pH-sensitive PEG-lipid derivative with an imine bond. These specially-designed nanoparticles exhibit pH-responsive release, internalization, and intracellular distribution in acidic pH of colon cancer HCT116 cells. These nanoparticles display low toxicity to blood and noncancerous intestinal cells. Delivery of miR-200 by SLN further increases the cytotoxicity of irinotecan-loaded liposomes against CRC cells by triggering apoptosis and suppressing RAS/ß-catenin/ZEB/multiple drug resistance (MDR) pathways. Using CRC-bearing mice, the in vivo results further indicate that irinotecan and miR-200 in pH-responsive targeting nanoparticles exhibit positive therapeutic outcomes by inhibiting colorectal tumor growth and reducing systemic toxicity. Overall, successful delivery of miR and chemotherapy by multifunctional nanoparticles may modulate ß-catenin/MDR/apoptosis/metastasis signaling pathways and induce programmed cancer cell death. Thus, these pH-responsive targeting nanoparticles may provide a potential regimen for effective treatment of colorectal cancer.

20.
J Nat Prod ; 82(11): 2972-2978, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31686504

RESUMO

A concise total synthesis of (±)-conolidine, a potent nonopioid analgesic, in 19% overall yield is described here. A gold(I)-catalyzed Conia-ene reaction (Toste cyclization) and a Pictet-Spengler reaction served as key transformations for assembling the 1-azabicyclo[4.2.2]decane core and defining the geometry of the exocyclic double bond. The activation energies of formation of the vinyl-gold intermediates were calculated and revealed a silyl enol ether with an unprotected indole moiety as a suitable precursor for the Toste cyclization. This six-step synthesis did not involve any nonstrategic redox manipulations.

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